Direct protein-lipid interactions shape the conformational landscape of secondary transporters
| Autor: | Mrinal Shekhar, Eamonn Reading, Chloe Martens, Emad Tajkhorshid, Argyris Politis, Antoni J. Borysik, Andy M. Lau, Paula J. Booth |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Escherichia coli -- metabolism
Membrane Proteins -- chemistry -- metabolism Monosaccharide Transport Proteins Protein Conformation Science Biophysics Molecular Dynamics Simulation medicine.disease_cause Cell Membrane -- metabolism Article Mass Spectrometry Escherichia coli Proteins -- chemistry -- metabolism Cell membrane Membrane Lipids chemistry.chemical_compound Molecular dynamics Molecular level Membrane Transport Proteins -- chemistry -- metabolism Escherichia coli medicine lcsh:Science Phosphatidylethanolamine Molecular switch Monosaccharide Transport Proteins -- chemistry -- metabolism Symporters Escherichia coli Proteins Cell Membrane Membrane Lipids -- chemistry -- metabolism Deuterium Exchange Measurement Membrane Proteins Membrane Transport Proteins Transporter Sciences bio-médicales et agricoles Symporters -- chemistry -- metabolism medicine.anatomical_structure chemistry lcsh:Q lipids (amino acids peptides and proteins) Protein Binding |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications Martens, C, Shekhar, M, Borysik, A, Lau, A M C, Tajkhorshid, E, Reading, E, Booth, P J & Politis, A 2018, ' Direct protein-lipid interactions shape the conformational landscape of secondary transporters ', Nature Communications, vol. 9, 4151 . https://doi.org/10.1038/s41467-018-06704-1 Nature communications, 9 (1 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-06704-1 |
| Popis: | Secondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane - yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations to understand how lipids regulate the conformational dynamics of secondary transporters at the molecular level. Using the homologous transporters XylE, LacY and GlpT from Escherichia coli as model systems, we discover that conserved networks of charged residues act as molecular switches that drive the conformational transition between different states. We reveal that these molecular switches are regulated by interactions with surrounding phospholipids and show that phosphatidylethanolamine interferes with the formation of the conserved networks and favors an inward-facing state. Overall, this work provides insights into the importance of lipids in shaping the conformational landscape of an important class of transporters. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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